Xi-Zhang Lin

Expression of vascular endothelial growth factor in normal liver and hepatocellular carcinoma: An immunohistochemical study

Angiogenesis is of vital importance during the development and progression of solid tumors. To examine the role of vascular endothelial growth factor (VEGF) in hepatocarcinogenesis, we evaluated the expression of peptide in normal human liver (n = 6) and in 36 cases of hepatocellular carcinoma (HCC). Immunoreactivity for VEGF was present in the extracellular matrix of the portal tracts in the normal and nontumor part of liver, but not in hepatocytes and bile duct epithelium. For HCC, variable amounts of VEGF were expressed in 13 cases (36.1%) of tumor cells. Using a logistic regression model, expression of VEGF was significantly associated with a higher proliferative index (P = .01) and sonographic portal vein thrombosis (P = .05). However, VEGF expression did not correlate with a biochemical liver profile, alpha-fetoprotein levels, histological grading, gender, or clinical stage of cirrhosis (P > 0.1, respectively). Log-rank test showed that evaluation of VEGF did not provide more prognostic information (P > .5) than that from tumor volume and portal vein thrombosis (P < .01, respectively). In addition, VEGF was always present in the fibrovascular stroma or pericellular matrix of HCC, although no strong relationship was observed with the expression of VEGF in tumor cells (P > .5). Our data suggested that expression of VEGF may characterize a progression toward higher proliferation in hepatocarcinogenesis in vivo. The relevance of VEGF existing in the extracellular matrix of the normal liver and HCC remains to be clarified.

Autophagy suppresses tumorigenesis of hepatitis B virus‐associated hepatocellular carcinoma through degradation of microRNA‐224

In hepatocellular carcinoma (HCC), dysregulated expression of microRNA‐224 (miR‐224) and impaired autophagy have been reported separately. However, the relationship between them has not been explored. In this study we determined that autophagy is down‐regulated and inversely correlated with miR‐224 expression in hepatitis B virus (HBV)‐associated HCC patient specimens. These results were confirmed in liver tumors of HBV X gene transgenic mice. Furthermore, miR‐224 was preferentially recruited and degraded during autophagic progression demonstrated by real‐time polymerase chain reaction and miRNA in situ hybridization electron microscopy after extraction of autophagosomes. Our in vitro study demonstrated that miR‐224 played an oncogenic role in hepatoma cell migration and tumor formation through silencing its target gene Smad4. In HCC patients, the expression of low‐Atg5, high‐miR‐224, and low‐Smad4 showed significant correlation with HBV infection and a poor overall survival rate. Autophagy‐mediated miR‐224 degradation and liver tumor suppression were further confirmed by the autophagy inducer amiodarone and miR‐224 antagonist using an orthotopic SD rat model. Conclusion: A noncanonical pathway links autophagy, miR‐224, Smad4, and HBV‐associated HCC. These findings open a new avenue for the treatment of HCC. (Hepatology 2014;59:505–517)

Splenic infarction after histoacryl injection for bleeding gastric varices

Gastric varix bleeding is a serious but relatively common complication in cirrhotic patients. Treatment is difficult not only because of the gastric intertwining venous network but also its isolated location in the cardia and fundus. The disappointing results with sclerosing agents in this situation have led to the introduction of tissue adhesive injection. A 93% success rate for initial hemostasis was achieved with N-butyl cyanoacrylate injection.1 The reported complications of this treatment include injection site ulcers, fever, chest pain, and thrombosis of the portal venous system.2 Splenic infarction as a complication had not been reported.

Clinical Significance of Ultrasonography, Computed Tomography, and Biochemical Tests in the Rapid Diagnosis of Gallstone-related Pancreatitis: A Prospective Study

Real-time ultrasonography (US), computed tomography (CT), and biochemical tests were prospectively performed to detect gallstones in 88 consecutive patients immediately after the onset of an attack of acute pancreatitis. The sensitivity of biochemical tests was 84.6% when the patients had three or more positives of five parameters [including serum bilirubin, alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGT), alanine transaminase (ALT), and alanine transaminase-aspartate transaminase (ALT-AST) ratio]. The sensitivity, specificity, and accuracy were 71.8, 98.0, and 86.4% for US, and 52.9%, 100%, and 79.5% for CT. The sensitivity, specificity, and accuracy were improved to 82.1, 100, and 93.2% by the combination of US and CT, and 94.9, 100, and 97.7% by the combination of US and biochemical tests. Adding CT to the combination of US and biochemical tests resulted in only a slight improvement in sensitivity and accuracy. In conclusion, a combination of US and biochemical tests can provide the best noninvasive method in rapidly detecting gallstones as an etiological factor in acute pancreatitis. Computed tomography is not cost-effective. A positive result of biochemical tests despite a negative finding in US calls for an intensive search for gallstones by further investigation with endoscopic retrograde cholangiography or repeated US examinations.

High Oxidative Stress Is Correlated with Frailty in Elderly Chinese

OBJECTIVES: To evaluate the relationship between oxidative stress and frailty in elderly people.

Spontaneous rupture of hepatocellular carcinoma : a review of 141 Taiwanese cases and comparison with nonrupture cases

We reviewed the records and statistics of 560 patients hospitalized with hepatocellular carcinoma (HCC) over a 5-year period. One hundred and forty-one patients (26%) had spontaneous rupture of their HCCs. Different characteristics of the rupture (R) and nonrupture (NR) groups were compared; there were statistically significant differences (p < 0.05) in the size of the tumor (R, 9.83 +/- 4.36 cm, and NR, 7.67 +/- 4.01 cm; p < 0.0001), and the minimal thickness of peritumor liver parenchyma (R, 0.03 +/- 0.20 cm, and NR, 0.30 +/- 0.70 cm; p < 0.001), the presence of the ¿hump sign¿ (R, 87.8%, and NR, 45.7%; p < 0.0001), and the minimal thickness of peritumor liver parenchyma (R, 0.03 +/- 0.20 cm, and NR, 0.30 +/- 0.70 cm; p < 0.001). The percentage of left-lobe tumors was significantly higher in the rupture group than in the nonrupture group (p < 0.05). In addition, the Child-Pughs score and serum transaminase levels were higher, and the prothrombin times more prolonged, in the rupture group. Factors that were not statistically significant included sex, age, etiology of cirrhosis, platelet count, portal vein thrombosis, and the presence of a varix. Multivariate logistic regression analysis indicated that the tumor size, the presence of a hump sign, and the Pughs score correlated the best with HCC rupture (p < 0.05). Ninety-four patients from the rupture group died during hospitalization. The mortality rate was 66.7%. We conclude that (a) spontaneous rupture of HCC is a likely sequel of progressive expansion of tumor that finally protrudes outside the liver surface and hemorrhages, (b) left-lobe tumor presents a higher risk of rupture, and (c) portal hypertension does not play a major role in the pathogenesis of tumor rupture.

Bleeding peptic ulcer--risk factors for rebleeding and sequential changes in endoscopic findings.

From September 1991 to December 1992, a prospective study was conducted to determine the risk factors and residual risk of rebleeding, and the evolutionary endoscopic changes in peptic ulcers that rebled. Emergency endoscopies were performed on 452 patients with haematemesis or a melaena, or both within 24 hours of admission. If the lesions were actively bleeding, then the patients were treated with injection sclerotherapy. A multivariate analysis of clinical, laboratory, and endoscopic variables of 204 patients with ulcer bleeding showed that hypovolaemic shock, a non-bleeding visible vessel, and an adherent clot on the ulcer base were independently significant in predicting rebleeding (p < 0.05). Considering these three factors according to the estimates of their regression coefficients showed that a non-bleeding visible vessel was the strongest predictor of rebleeding. The study of the residual risk of rebleeding after admission showed that most rebleeding episodes (94.1%), including all associated with hypovolaemic shock, surgical treatment, and death, occurred within 96 hours of admission. After this time, the residual risk of rebleeding was less than 1%. Study of the changes in endoscopic findings before and after rebleeding illustrated that all ulcers with a visible vessel or adherent clot showed at follow up endoscopy were derived from ulcers with initial major stigmata. It is concluded that hypovolaemic shock, a non-bleeding visible vessel, and an adherent clot on an ulcer base are of independent significance in predicting rebleeding. Observation for 96 hours is sufficient to detect most rebleeding episodes after an initial bleed from peptic ulcer.

Bacterial density of Helicobacter pylori predicts the success of triple therapy in bleeding duodenal ulcer

BACKGROUND We studied whether different initial bacterial densities of Helicobacter pylori would alter the eradication rate of H. pylori by triple therapy (amoxicillin 500 mg t.i.d. and metronidazole 500 mg t.i.d. for 14 days; bismuth subcitrate 120 mg t.i.d. for 28 days) in patients with duodenal ulcer bleeding. METHOD One hundred thirty-six cases with duodenal ulcer bleeding and H. pylori infection (proved by rapid urease test and histology during emergency endoscopy) were studied. One hundred twenty-seven of these patients completed a course of triple therapy. In each case, anti-H. pylori IgG titer, gastric biopsies for H. pylori density (score 1 to 5), and evaluation of severity of gastritis were collected at the first endoscopy and 1 month after completion of the triple therapy. RESULTS The ulcer healing rate was 84.3% (107 of 127) at the time of the second evaluation. The eradication rate of H. pylori was 76.4% (97 or 127). Eradication for H. pylori failed in 30 cases. In these eradication failure cases, initial serologic titer and density of H. pylori were higher than those of eradication success cases. The eradication rate of H. pylori decreased as the initial density of H. pylori increased (density of H. pylori: 1, 88.3%; 2, 83.8%; 3, 74.2%; 4, 68%; 5, 50%). At the second evaluation, the serologic titer was lower and continued to decline in eradication success cases whose mean residual titer ratio (100% x follow-up titer/initial titer) was lower than that of eradication failure cases (57.1% +/- 14.6% vs 107.1% +/- 24.1%, p < 0.001). The mean residual titer ratio also disclosed an upward trend as the density of H. pylori increased (density of H. pylori 1 to 5: 57.5%, 66.6%, 73.5%, 75.3%, 81.8%, respectively). CONCLUSIONS We suggest routine gastric biopsy to detect both the presence of H. pylori and its density inasmuch as quantitative results may predict the usefulness of triple therapy. The higher the H. pylori density, the less effective triple therapy will be at successful eradication of H. pylori.

When to discharge patients with bleeding peptic ulcers : a prospective study of residual risk of rebleeding

BACKGROUND From January 1993 to December 1994, we conducted a prospective study to investigate the evolutionary change of rebleeding risk in bleeding peptic ulcers. To obviate possible confounding factors that would influence decision making for discharge of patients, subjects with coexistent acute illnesses, systemic bleeding disorders, alcoholism, and use of nonsteroidal anti-inflammatory drugs were excluded. METHODS Emergency endoscopies were performed in patients with hematemesis or a melena within 24 hours of admission. Ulcer lesions were divided into six categories according to endoscopic findings. The residual risks of rebleeding of each type of ulcers were calculated for 10 days, and the critical point of acceptable rebleeding risk after discharge was set at 3%. RESULTS Three hundred ninety-two patients with bleeding peptic ulcers completed the study. The ulcers, characterized by clean bases, red or black spots, adherent clots, nonbleeding visible vessels without local therapy, nonbleeding visible vessels with local therapy, and bleeding visible vessels with local therapy took 0, 3, 3, 4, 4, and 3 days, respectively, to decrease rebleeding risk to below the critical point. All episodes of fatal rebleeding (n = 4) occurred within 24 hours after admission. CONCLUSIONS Patients with clean-based ulcers can be discharged in the first day of admission. The optimal duration required for hospitalization of patients with ulcers characterized by nonbleeding visible vessels at initial endoscopy is 4 days. The remaining patients with ulcers marked by other bleeding stigmata may be discharged after a 3-day observation.

Serum amylase, isoamylase, and lipase in the acute abdomen: their diagnostic value for acute pancreatitis

We evaluated the diagnostic value of serum amylase, isoamylase, and lipase for the diagnosis of acute pancreatitis from sera of patients with acute abdominal pain. Comparison was first made in condition A between 32 patients with image-proven pancreatitis and 414 patients with nonpancreatic acute abdomen (the control group), then in condition B, between 62 pancreatitis patients with or without image proof and the control group. We found (a) that patients with image-proven pancreatitis suffer a more severe clinical course than those without; (b) that the sensitivity, positive predictive value, and accuracy in condition B are higher than in condition A at any cutoff level; (c) that none of the enzyme assays is specific at the upper reference limit, but their diagnostic yields are much improved by raising cutoff levels to about three or four times the upper limit; and (d) that at these selected cutoff levels, amylase had a diagnostic value similar to p-isoamylase or lipase in both conditions (sensitivity 84% and 92% for amylase in conditions A and B, respectively; specificity 98% and 98%; positive predictive value 75% and 90%; negative predictive value 99% and 99%; accuracy 91% and 97%). In conclusion, at an appropriately selected cutoff level, amylase can be effectively used as the first-line test and isoamylase or lipase as adjunct tests for acute abdominal conditions.